Probe for blood gas sensing

ABSTRACT

In a blood gas sensing probe, a cylindrical sleeve contains an optical fiber. The end of the optical fiber is withdrawn into the sleeve thereby creating a receptacle at the end of the sleeve. A sensitive dye, HOPSA for example, is encapsulated in a gel and deposited in the receptacle to form the probe. In making the probe, the end of the optical fiber is in the same plane as the end of the sleeve in which it is placed. The dye and gel contact the combined ends of optical fiber and sleeve. The fiber is withdrawn into the sleeve thereby creating a vacuum which is filled by the dye and gel.

BACKGROUND OF THE DISCLOSURE

This invention relates to a probe for sensing pH of the blood althoughthe probe constructed in accordance with the principles of the presentinvention could be used for sensing other blood gases or electrolytes.

The concept of mounting a blood gas sensitive dye on the end of anoptical fiber, exciting the dye with light passing through the opticalfiber and measuring the partial pressure of the blood gas by measuringsome aspect of the excited fluorescent dye is known. See, for example,U.S. Pat. No. 31,879, issued May 7, 1985, Lubbers et al, and U.S. Pat.No. 4,200,110, issued Apr. 29, 1980, Peterson et al. This concept is ofgreat importance to the medical profession, for its permits the realtime monitoring of a patient's condition during medical/surgicalprocedures.

In spite of the very considerable need for a probe tiny enough to beinsertable into the blood vessels of a patient, no probe has enjoyed anymeasurable commercial success.

An objective of the present invention has been to provide an improvedprobe and a method of making it.

Another more specific objective of the present invention has been toprovide a method, and an article produced from the method, for placing asensor/gel on the end of a tiny optical fiber. The optical fiber in theillustrated form of the invention is 0.009" in diameter.

The objectives of the invention are obtained by providing a sleevearound the optical fiber. Initially, the ends of the sleeve and opticalfiber coincide, that is to say, they lie in the same plane. Thefiber/sleeve combination is placed into a drop of sensor matrix, i.e., amixture containing a fluorescent indicator, the monomer, andpolymerization initiator, which is curable to provide a sensor gel. Thefiber is pulled back with respect to the sleeve thereby creating apocket and a vacuum in the pocket which is immediately filled by theflow of the sensor matrix into the thus formed pocket. Thus, it is thata very tiny volume (a cylinder approximately 0.009" long and 0.010"diameter) of the sensor matrix is mounted on the end of an optical fiberwithout the possibility of oxygen occurring at the interface between theend of the fiber and the sensor matrix. The sensor matrix is then curedto provide a stable sensor gel on the end of the probe.

Curing the sensor matrix using conventional heating means to provide thedesired sensor gel requires heating the sensor matrix in an oven forthree to five hours. In accordance with one aspect of the presentinvention, the sensor matrix is cured by subjecting it to ultravioletlight for a period of about twenty seconds. The particular combinationof components in the sensor which permits this twenty-second ultravioletlight cure includes a derivative of HOPSA (HOPSA is an acronym for8-Hydroxy-1,3,6-pyrenetrisulfonic acid trisodium salt), acrylamidemonomers, and an azo-polymerization initiator.

It was necessary to prepare a derivative of the HOPSA indicator thatcontained an alkene function which would copolymerize with theacrylamide monomers of which the hydrogel portion of the sensor gel ismade. The hydrogel is the support material in which the indicator iscopolymerized and held while still allowing molecular contact with theanalyte to be measured. Through numerous tests, a HOPSA derivative wasfound which appeared to be held very strongly within the polyacrylamidehydrogel upon curing of the sensor matrix. That derivative,di-substituted HOPSA (2-propenyl)sulfonamido, which for ease ofreference will be referred to hereinafter as "di-substituted HOPSA," hasthe following structural formula: ##STR1##

Another aspect of the present invention involves creating andmaintaining an oxygen-free atmosphere throughout the curing(polymerization) process in order to eliminate the presence of oxygenwhich competes against the acrylamide monomers for the initiator. Thisnot only slows the cure of the polyacrylamide, it may also detrimentallyaffect the sensitivity of the sensor gel.

Another feature of the present invention resides in the mounting of afiber in a Y-connector which, in turn, can be connected to a catheterthrough which the optical fiber and sleeve, with the sensor on its end,can be inserted into the blood vessel of a patient.

BRIEF DESCRIPTION OF THE INVENTION

The several objectives and features of the present invention will becomemore readily apparent from the following detailed description taken inconjunction with the accompanying drawings in which:

FIG. 1 is a diagrammatic view of the sensor as applied to a patient'sarm;

FIGS. 2 and 3 are diagrammatic views of the sensor and method of makingit; and

FIG. 4 is a diagrammatic view of the method of curing the sensor gelafter it has been drawn into the sensor tip.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIG. 1, the sensor is shown as applied to a blood vessel ina patient's arm. A catheter 10 is inserted in the patient's arm. Thecatheter has a male Luer connection 11 on one end. A Y connector 15 hasa female Luer connection 16 on one end adapted to receive the maleconnection 11. An elongated sensor 20 passes through the main branch 21of the Y connector and is sealed there by a cement such ascyanoacrylate, indicated at 22. The sensor 20 passes through thecatheter 10 which is connected to the Y-connector 15 by the Luerconnection 11, 16.

The Y connector 15 has a branch 25 which is connected to a salinesolution 26 which is slowly passed through the catheter to help maintainthe sensor free from blood clotting. The sensor 20 has a section 30upstream from the plastic seal 22 that is connected to a monitor 31. Themonitor 31 contains the light source that is directed through theoptical fiber to a sensor gel in the sensor tip 32 to excite thefluorescent HOPSA-derivative indicator held in the gel. The intensity ofexcitation is measured by the monitor and that provides a continuousmeasure of the pH in the patient's blood. See the Boiarski U.S. patentapplication Ser. No. 07/282,961, filed Dec. 2, 1988, whose disclosure isincorporated herein by reference and forms a part of the application.This application discloses a method of excitation and measuring thelevel of intensity.

FIGS. 2 and 3 disclose the details of the sensor tip and its method ofapplying the sensor matrix to it. An optical fiber 40 having a length asdesired for the particular application is clad in a jacket 41. Theoptical fiber is preferably 0.009" in diameter. The fiber is preferablya 200/225 μ silica optic fiber. A sleeve consisting of fused silicacapillary tubing 42 is slidably mounted on a free end 43 of the opticfiber 40. The sleeve 42 has an I.D. of 0.010", thereby providing a snug,substantially air-free, fit between the fiber 40 and the sleeve 42. Thesleeve 42 has an end surface 44 and the optic fiber 40 has an endsurface 45, those end surfaces being substantially coextensive with eachother, that is, lying in the same plane, at the beginning of theoperation to apply the dye to the end 45 of the optic fiber.

The sensor matrix liquid mixture containing the HOPSA-derivativeindicator, monomers and polymerization initiator is formed as describedhereafter. A drop 50 of that sensor matrix is applied across thesurfaces 44, 45 of the sleeve 42 and optic fiber 40, respectively. Theend 43 of the optic fiber is then slid inwardly with respect to thesleeve a distance of about 0.009" to create a cavity or receptacle 51whose diameter is 0.010" and whose length is 0.009". The creation ofthat receptacle 51 causes the creation of a vacuum which drives thesensor matrix into the receptacle. Capillary action along thecylindrical space between the sleeve 42 and fiber 40 causes the sensormatrix to flow by capillary action into that space, thereby driving outthe air. The air is permitted to escape through a gap 52 between thesleeve 42 and the cladding 41 around the fiber. That space 52 isthereafter sealed by applying the cyanoacrylate to it as indicated at53.

The sensor matrix must be cured to provide a stable sensor gel.Conventionally, sensor matrices of the type employed herein are cured bybaking in an oven over a period of three to five hours. In accordancewith the present invention, the matrix is cured by subjecting it toultraviolet light for a period of about twenty seconds as shown in FIG.4. To this end, a curing chamber 60 is formed by a Pasteur pipet. Alight gun 61 and power supply 62 is capable of delivering a highintensity ultraviolet light at an intensity of 50 mW/CM² onto the sensor20 in curing chamber 60. The curing is performed in an oxygen-freeatmosphere provided by delivering argon from a supply 65 to the curingchamber 60. The argon is passed through a flask 66 of de-ionized water67 in order to humidify it. The atmosphere surrounding the tip in thepipet is oxygen-free. Elimination of oxygen is critically important, forotherwise the oxygen, which competes against the acrylamide monomers forthe initiator, will slow the curing process and decrease the sensitivityof the sensor.

The HOPSA-derivative/hydrogel sensor matrix was prepared by firstpreparing and combining a sensor solution and an initiator solution. Thesensor solution was prepared by completely dissolving (for five to tenminutes) the following dry reagents in 0.006L ofTris(hydroxymethyl)aminomethane buffer (pH=8.75@25° C.; available fromPolysciences, Inc.):

1.8750 g Acrylamide (ultra pure);

0.0625 g N,N'-Methylene-bis-acrylamide (ultra pure); and

0.009 g di-substituted HOPSA (2-propenyl) sulfonamido

(prepared by Battelle, Columbus Div.)

The preferred concentration of the di-substituted HOPSA in the hydrogelsolution, found to give the best combination of stability and highsensitivity of the resulting sensor gel, was 1.5 mg of di-substitutedHOPSA per 1.0 mL of hydrogel solution.

Once the above reagents were completely dissolved in the buffer, thesolution was filtered through a filter having a 0.45 micron pore size toremove any contaminants, e.g., dust. Following filtration, the solutionwas purged with argon (industrial grade) for approximately five minutesto expel any oxygen from the solution.

The initiator solution was prepared by dissolving 0.32 g of VA-044 in0.01L of distilled water. VA-044 is the trade name of Wako Pure ChemicalIndustries, Ltd. for their Azo-polymerization initiator2,2'-Azobis(N,N'-dimethyleneisobutyramidine) dihydrochloride, which hasa molecular weight of 323.33. While VA-044 is the preferredpolymerization initiator, V-50 may also be used. V-50 is the trade nameof Wako Pure Chemical Industries, Ltd. for the initiator2,2'-Azobis(2-amidinopropane)dihydrochloride, which has a molecularweight of 271.27.

Subsequently, the di-substituted HOPSA/acrylamide hydrogel sensor matrixwas prepared by adding 100 uL of the initiator solution to the sensorsolution, which was placed in a Kimble 25 mL EPA vial with an open topclosure and polytetrafluoroethylene-faced silicone rubber septum. Thismixture was then purged with argon for approximately five minutes todispel any oxygen present. Sealed in this manner, the sensor-initiatorsolution can be stored in a freezer for extended periods of time with noill effects.

The sensor gel was then prepared by curing the sensor matrix asdescribed hereinabove.

From the above disclosure of the general principles of the presentinvention and the preceding detailed description of a preferredembodiment, those skilled in the art will readily comprehend the variousmodifications to which the present invention is susceptible. Therefore,we desire to be limited only by the scope of the following claims andequivalents thereof:

We claim:
 1. A blood probe comprising:an optical fiber having two ends,one of which is a distal end, a cylindrical sleeve surrounding saidfiber and extending beyond said distal end of said fiber, therebycreating a receptacle at the distal end of said fiber, a sensitive dyebound in a cured gel disposed in said receptacle and in intimate contactwith the distal end of said optical fiber and free of oxygen at theinterface between said dye and the distal end of said fiber, said dyebeing exposed at the end of said sleeve for contact with blood.
 2. Aprobe as in claim 1 in which the length of said receptacle beyond saidend of said fiber is approximately equal to the diameter of said fiber.3. A probe as in claim 1 in which said dye is pH-sensitive and is HOPSAbound in a cured gel matrix.
 4. A probe as in claim 1 furthercomprising,said sleeve having a proximal end, said optical fiber havinga protective cylindrical jacket spaced from said proximal end of saidsleeve, and means for forming a seal between said proximal end and saidcylindrical jacket.
 5. A blood probe comprising:an optical fiber havingtwo ends, one of which is a distal end, a cylindrical jacket claddingsaid optical fiber while leaving an end portion of said fiber projectingbeyond said jacket, a sleeve surrounding said projecting end portion ofsaid fiber, said sleeve projecting beyond said distal end of said fiberto create a receptacle having the distal end of said fiber as itsbottom, a sensor matrix formed of a sensitive dye bound in a cured geldisposed in said receptacle and having one end of said matrix inintimate contact with the distal end of said fiber and the other end ofsaid matrix free for contact with blood, said sleeve beinglongitudinally spaced from said cylindrical jacket, and an adhesivejoining said sleeve to said jacket.